慢性间断性缺氧对帕金森病模型小鼠认知功能及海马神经元结构的影响

Effects of chronic intermittent hypoxia on the cognitive function and neuron structure of hippocampus in mouse model of Parkinson's disease

目的探讨慢性间断性缺氧对帕金森病模型小鼠认知功能、海马神经元结构及突触素表达水平的影响。方法采用百草枯腹腔注射联合慢性间断性缺氧制备帕金森病伴睡眠障碍小鼠模型,通过电迷宫和跳台实验评价其学习和记忆能力,HE和Nissl染色观察海马神经元形态及数目变化、免疫组织化学染色检测海马神经元突触素表达水平、电子显微镜观察海马神经元超微结构。结果与对照组比较,百草枯组、慢性间断性缺氧组及其联合组小鼠学习和记忆成绩显著下降(均P<0.05),电迷宫和跳台实验总反应时间延长、错误反应次数增加;Nissl染色阳性神经元数目减少、突触素表达水平升高。光学显微镜和电子显微镜观察显示,百草枯组、慢性间断性缺氧组及其联合组小鼠海马神经元均有不同程度损害,但以百草枯联合慢性间断性缺氧组最为明显(均P=0.000)。结论慢性间断性缺氧可加重百草枯所致帕金森病模型小鼠的学习和记忆障碍,可能与海马神经元结构损害、突触功能减弱有关。

Objective To investigate the effects of chronic intermittent hypoxia （CIH） on the cognitive function, neuron structure and synaptophysin （Syn） expression of the hippocampus in mouse model of Parkinson＇s disease （PD）. Methods A hypoxia-reoxygen device was used to prepare the model of CIH. Meanwhile, the PD mouse model was built by intraperitoneal injection of paraquat （PQ）. The cognitive function was evaluated by Y-type electric maze and step-down test. Syn expression in the hippocampus was estimated by immunohistochemistry. The neuron structure in the hippocampus was observed by HE staining, Nissl staining and the electron microscope. Results Comparing to control group, a significant decrease was found in learning and memorizing performance （P 〈 0.05, for all） and the amount of neuron, while a significant increase was seen in total reaction time （TRT） and error reaction （ER） in Y-type electric maze and step-down test and the gray value of Syn in the hippocampus in PQ, CIH, and PQ ＋ CIH groups. Various degrees of anomaly were observed in neuron structure of hippocampus by HE staining, Nissl staining and electron microscopy in PQ, CIH, and PQ ＋ CIH groups, while presented most obviously in the latter group. Conclusion The PQ- induced impairment of cognitive function in PD model mice was aggravated by CIH, which may be related to the damage of neuron structure and the decrease of synaptic function in hippocampus.